Acute effects of high-dose thyrotropin releasing hormone infusions in Alzheimer's disease

Thyrotropin releasing hormone (TRH) was administered intravenously to ten patients with Alzheimer's Disease (AD) in a high-dose paradigm, thought to maximize central nervous system effects and potentially produce facilitation of cholinergic function, a known property of the neuropeptide. Acute effects of TRH on behavioral, cognitive and physiologic measures were assessed after patients received 0.1 mg/kg TRH, 0.3 mg/kg TRH and placebo, the higher TRH dose and placebo being given in a randomized, double-blind fashion. Patients showed statistically significant increases in arousal and improvement in affect, as well as a modest improvement in semantic memory, all after receiving the higher TRH dose. Both TRH doses produced transient rises in systolic blood pressure, with no effect on diastolic blood pressure, heart rate or temperature. This study suggests that high-dose TRH can be safely administered to AD patients and is neurobehaviorally active; further studies are needed to determine the extent and mechanism of the cognitive and psychobiological properties of this peptide in AD and other neuropsychiatric disorders.     

142Effects of Low‐Frequency Ultrasound Applied In Vitro to Highly Antibiotic‐Resistant Acinetobacter Isolates Recovered From Soldiers Returning From Iraq

Abstract  Brooke Army Medical Center isolated 25 highly antibiotic‐resistant Acinetobacter ssp . (primarily A. baumannii ) from wounded soldiers returning from Iraq. Concern about effective treatment of these organisms led our institution to begin investigating low‐frequency ultrasound (LFU) as a method of increasing the effectiveness of antibiotics on A.baumannii in wound management. Studies have suggested that LFU applied in conjunction with antibiotics may increase their overall effectiveness. We hypothesize that combining antibiotics with LFU may be an effective method of wound management and that this combination may be synergistic in its overall effect. In this initial work, we wanted to determine if sonocation would have an effect on our organism of interest, A. baumannii . We selected several organisms, both gram positive and gram negative, that have been shown to be killed by sonocation ( E. coli, S. aureus , and S. pyogenes ) and added three highly resistant A. baumannii isolates. Bacterial death was measured by both colony counts after 24 hours of growth and acridine orange staining using a standard protocol.
Colony counts were significantly reduced by sonocation. Furthermore, A.'baumannii colony counts were also greatly reduced by sonocation. Actual cell destruction was also visualized using acridine orange staining. Our data support the assertion that sonocation has an antibacterial effect on some bacteria, including A. baumannii . Our next step is to add antimicrobial agents and determine if their effectiveness can be increased by sonocation.     

Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy.

OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP remains controversial. METHODS: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP.     

Comparison of novel computer detectors and human performance for spike detection in intracranial EEG.

OBJECTIVE: Interictal spikes in intracranial EEG (iEEG) may correlate with epileptogenic cortex, but review of interictal iEEG is labor intensive. Accurate automated spike detectors are necessary for understanding the role of spikes in epileptogenesis. METHODS: The sensitivity, accuracy and reproducibility of three automated iEEG spike detectors were compared against two human EEG readers using iEEG segments from eight patients. A consensus set of detections was generated for detector calibration. Spike verification was calculated after both human EEG readers independently reviewed all detections. RESULTS: Humans and two of the three automated detectors demonstrated comparable accuracy. In four patients, automated spike detection sensitivity was >70% and accuracy was >50%. In the remaining four patients, EEG background morphology resulted in poorer performance. Blinded human verification accuracy was 76.7+/-6.6% for computer-detected spikes, and 84.5+/-4.1% for human-detected spikes. CONCLUSIONS: Automated iEEG spike detectors perform comparably to humans, but sensitivity and accuracy are patient dependent. Humans verified the majority of computer-detected spikes. SIGNIFICANCE: In some patients automated detectors may be used for mapping spike occurrences in epileptic networks. This may reveal associations between spike distribution, seizure onset, and pathology.     

Nonimmunological alterations of glomerular filtration by s-PAF in the rat kidney

Rat kidneys were isolated and perfused with a cell-free perfusion buffer containing 4% albumin. Infusion of platelet activating factor (s-PAF) into the isolated perfused kidney caused a dose-dependent fall in renal vascular resistance (RVR): 12 +/- 6% at 10 nM s-PAF, 18 +/- 3% at 100 nM s-PAF and 20 +/- 7% at 1 microM s-PAF. Glomerular filtration rate fell by 32 +/- 5% at 10 nM, 38 +/- 6% at 100 nM, and 52 +/- 10% at 1 microM. s-PAF (50 nM) increased urinary protein excretion after 20 minutes. Because GFR fell to a greater extent than RVR, possible changes in glomerular permeability after s-PAF treatment were assessed morphologically using native ferritin. After s-PAF treatment (100 nM), the number of ferritin particles/micron2 increased from 1.2 +/- 0.9 (control) to 795 +/- 69 in the glomerular basement membrane (GBM) and from 0.2 +/- 0.06 (control) to 98 +/- 29 in lamina rara externa (LRE). To quantitate changes in fixed anionic charges, polyethylenimine (PEI) was quantitated morphologically in GBM. No significant change between s-PAF treated and untreated kidneys was seen. s-PAF did not alter the sialoglycoprotein pattern in the perfused kidney as assessed by lysozyme staining. These results are in contrast to findings with s-PAF in vivo where in addition to increased glomerular permeability, a reduction of fixed anionic charges is seen.(ABSTRACT TRUNCATED AT 250 WORDS)